Delivery of Active Agents Using a Chocolate Vehicle

ABSTRACT

This invention provides edible compositions comprising pharmaceutically or nutraceutically active agents in particulate form homogeneously dispersed in a fat matrix, such as chocolate or chocolate compound coating.

This application is a divisional application of U.S. patent applicationSer. No. 11/437,371, filed May 19, 2006, the contents of which arehereby incorporated by reference in their entirety.

FIELD OF INVENTION

The present invention relates generally to compositions for oralconsumption comprising one or more active agents. More particularly, theinvention relates to the use of a fat matrix, such as chocolate, fordelivering active agents.

BACKGROUND OF THE INVENTION

The continuing advances in medical and nutritional science have led tothe development of a large number of pharmaceutical and nutraceuticalagents which are prescribed or recommended for a variety of indications.In many cases, the efficacy of such agents in clinical settings isunquestioned. However, the established clinical efficacy of an agent isnot always realized in the population at-large, owing in part to poorpatient compliance.

For example, dietary calcium is an essential nutrient which has beenestablished to play a vital role in building healthy teeth and bones,blood clotting, muscle contraction, and nerve function. In addition tothese benefits, it has been suggested that calcium reduces the risk ofrecurrence of colon polyps. see Baron J. A. et al. New England Journalof Medicine 1999; 340: 101-107. Most notably, calcium reduces the riskof bone loss caused by osteoporosis in both men and women. Notsurprisingly, physicians recommend calcium supplements more than anyother dietary supplement.

Despite these advantages, it has been estimated that half of allAmericans do not consume sufficient amounts of calcium. More troubling,80% of women, the group at highest risk for developing osteoporosis, donot consume enough calcium.

This deficiency is due in part to the large daily intake of calcium thatis suggested by physicians. The United States Recommended DailyAllowance (“USRDA”) of calcium for adults is 800 to 1,400 mg. TheNational Academy of Sciences, Institute of Medicine recommends calciumintakes of 1,200 mg per day for people over 50 years of age and 1,300 mgper day for people under 19 years of age. In order to meet theserecommendations, approximately 2.5 to 3.5 g of calcium carbonate, themust common source of dietary calcium, must be consumed daily to meetthe recommendations. However, it is not practical to make tabletscontaining such large amounts of calcium carbonate. Consequently,supplemental calcium regimens typically comprise administering twotablets daily of 500 to 600 mg of calcium. Conventional calcium tabletsare therefore very large and difficult or uncomfortable to swallow. Thisproblem is exacerbated when excipients are also present in theformulation. As with any solid dose pharmaceutical or nutraceutical,large tablet size often leads to poor patient compliance. In addition tocalcium supplements, this disadvantage is commonly encountered withtablets having large amounts of active ingredients, such asmulti-vitamins and high-dose pharmaceuticals.

In other cases, poor patient compliance may result from theobjectionable taste or consistency associated with certain activeingredients. For example, the active agent may be perceived as pasty,dry, dusty, chalky, bitter or may possess an unpleasant aftertaste.Vitamin B complex, for example, is particularly associated withunpleasant taste.

In view of these problems, there have been numerous attempts to deliveractive agents in forms which are less objectionable to the consumer. Oneapproach has been to formulate smaller tablets which are morecomfortable to swallow. In this regard, special mention may be made ofU.S. Patent Pub. No. US2005/0025811 to Levin et al. which disclosescalcium carbonate tablets having volumes which are about 20 to about 35%smaller than conventional calcium carbonate tablets.

Other approaches have involved delivering active agents in the form ofchewable confections. This approach has received considerable attentionbecause size restraints are not as important as in other oral dosageforms and flavorants may therefore be added in sufficient quantities tomask unpleasant tastes characteristic of the active agent. For example,commercial chewable calcium supplements based on carbohydrate matricesare well known. There are nonetheless certain disadvantages associatedwith these products. Notably, carbohydrate matrices provide ahydrophilic environment which may promote microbial activity andconsequently reduce shelf-life or require the presence of antimicrobialagents in the formulation.

There is a continuing need in the art for oral dosage forms fordelivering active agents. It is therefore an object of the presentinvention to provide comestible compositions comprising active agentswhich present desirable organoleptic attributes (i.e., taste andtexture) to the consumer. It is also an object of the present inventionto provide comestible compositions comprising active agents which maskunpleasant tastes and textures associated with the active agents. It isfurther an object of the present invention to provide comestiblecompositions comprising active agents which are resistant to microbialactivity.

SUMMARY OF THE INVENTION

In accordance with the foregoing objectives and others, the presentinvention provides compositions comprising chocolate or chocolatecompound as a delivery vehicle for active agents. Chocolate iswell-suited as a vehicle for delivering active agents in many respects.For example, the organoleptic characteristics of chocolate are excellentfor masking unpleasant flavors associated with some active agents andimparting a smooth and creamy texture to compositions of active agentsthat are otherwise undesirably gritty. Chocolate is also a substantiallyanhydrous medium and is therefore resistant to microbial growth and tohydrolysis of water-sensitive active agents. Despite these advantages,chocolate has not found commercial acceptance as a pharmaceutical ornutraceutical delivery vehicle, owing in part to the difficulty offormulating chocolate compositions which comprise particulate activeagents. It has surprisingly been found that chocolate dosage formscomprising pharmaceutically or nutraceutically effective amounts ofparticulate active agents may be formulated by carefully controlling theparticle size of the particulate active agent.

In one aspect of the invention, compositions are provided which comprise(i) a particulate composition comprising one or more active agents, and(ii) a vehicle comprising a fat matrix. The particulate composition hasa median particle diameter between about 1 μm (micron) and about 25 μm,preferably between about 10 μm and about 13 μm. The fat matrix has amelting point between about 30° C. and about 49° C. The particulatecomposition is typically homogeneously dispersed throughout the fatmatrix.

In another aspect of the invention, a dietary supplement is providedcomprising at least about 25% by weight calcium carbonate powder havinga median particle size between about 1 μm and about 25 μm homogeneouslydispersed throughout a fat matrix having a melting point between about30° C. and about 49° C.

In a further aspect of the invention, an edible composition is providedcomprising: (i) a particulate composition comprising one or more activeagents, the particulate composition having a median particle diameterbetween about 10 μm and about 13 μm; and (ii) a vehicle comprising a fatmatrix, the fat matrix having a melting point between about 30° C. andabout 49° C.; wherein the particulate composition is dispersedhomogeneously throughout the fat matrix. The particulate composition,which preferably includes calcium carbonate, may have a distribution ofparticle diameters wherein about 50% or more of the bulk volume of theparticulate composition has a particle size between about ±66% of themedian diameter and about 30% or more of the bulk volume has a particlesize between about ±33% of the median diameter.

In yet another aspect of the invention, a dietary supplement is providedcomprising a fat matrix having a melting point between about 30° C. andabout 49° C.; wherein a 7 g serving of the dietary supplement comprises:(i) between about 1 and about 5,000 mg of calcium carbonate powderhaving a median particle diameter between about 1 μm and about 25 μm;(ii) one or more vitamins selected from the group consisting of: between1 and about 35,000 IU (International Unit) of vitamin A; between 1 andabout 1,000 mg of vitamin C; between 1 and about 4,000 IU of vitamin D;between 1 and about 450 IU of vitamin E; between 1 and about 250 mcg(microgram) of vitamin K; between 1 and about 15 mg of vitamin B-1(thiamin); between 1 and about 17 mg of vitamin B-2 (riboflavin);between 1 and about 200 mg of vitamin B-3 (niacin); between 1 and about100 mg of vitamin B-5 (pantothenic acid); between 1 and about 30 mg ofvitamin B-6 (pyridoxine); between 1 and about 4,000 mcg of vitamin B-9(folic acid); between 1 and about 250 mcg of vitamin B-12 (cobalamin);between 1 and about 1,000 mcg of vitamin H (biotin); or combinationsthereof; and (iii) one or more minerals selected from the groupconsisting of: between 1 and about 180 mg of iron; between 1 and about1,100 mg of phosphorous; between 1 and about 1,500 mcg of iodine;between 1 and about 4,000 mg of magnesium; between 1 and about 150 mg ofzinc; between 1 and about 600 mcg of selenium; between 1 and about 20 mgof copper; between 1 and about 20 mg of manganese; between 1 and about2,000 mcg of chromium; between 1 and about 750 mcg of molybdenum; orcombinations thereof; wherein the calcium carbonate powder, vitamins,and minerals are homogeneously dispersed throughout the fat matrix.

In an additional aspect of the invention, a dietary supplement isprovided comprising a chocolate or chocolate compound coating matrixhaving a melting point between about 35° C. and about 40° C. comprisingone or more active agents selected from the group consisting of: vitaminA, vitamin C, vitamin D, vitamin E, vitamin K, thiamin, riboflavin,niacin, vitamin B6folic acid, vitamin B12biotin, pantothenic acid,calcium, phosphorus, iodine, magnesium, zinc, selenium, copper,manganese, chromium, molybdenum, chloride, potassium, boron, nickel,silicon, vanadium, lutein, lycopene, iron, tin, ginseng root, and ginkgobiloba leaf; wherein the one or more active agents are dispersedhomogeneously throughout the chocolate or chocolate compound coatingmatrix and collectively comprise at least about 20% by weight of thechocolate or chocolate compound coating matrix; and wherein the apparentviscosity of the chocolate or chocolate compound coating matrixcomprising the one or more active agents, in the molten state, isbetween about 500 and about 100,000 cP (centipoises) at 50° C. and aspindle rate of 20 RPM when measured on a spindle viscometer.

These and other aspects of the invention may be more clearly understoodby reference to the following detailed description of the invention andthe appended claims.

DETAILED DESCRIPTION OF THE INVENTION

In the following description of the invention, it is to be understoodthat the terms used have their ordinary and accustomed meanings in theart, unless otherwise specified. The term “active agent” is intended tobroadly refer to any substance administered to an individual to achievea biological effect. The term “active agent” includes, withoutlimitation, pharmaceuticals, nutraceuticals, vitamins, minerals, herbalremedies, and the like.

The compositions of the invention comprise a fat matrix as a deliveryvehicle for an active agent. In the broadest aspects of the invention,any fat is contemplated to be suitable, including but not limited to,saturated fats, mono-unsaturated fats, polyunsaturated fats, trans fats,and combinations thereof Preferably, the fat is one which is solid atroom temperature. In this regard, particular mention may be made ofsaturated fats comprising fatty acids having between 12 and 18 carbonatoms such as lauric, myristic, stearic, and palmitic acids, including,without limitation, vegetable shortening, butter, milk fat, coconut oil,palm oil, palm kernel oil, and hardened or hydrogenated vegetable oils.A particularly interesting fat is cocoa butter.

The skilled artisan will recognize that cocoa butter comprises varyingamounts of palmitic-oleic-palmitic (POP), palmitic-oleic-stearic (POS),stearic-oleic-stearic (SOS), palmitic-oleic-oleic (POO), andstearic-oleic-oleic (SOO) triglycerides, depending on the country oforigin. Cocoa butter is known to solidify into six polymorphic forms(often numbered as Forms I-VI), each of which comprises a fat matrix(i.e., a three-dimensional arrangement of fat molecules) that issubstantially crystalline. Each of the forms has a different meltingrange, as shown in Table 1.

TABLE 1 MELTING RANGES OF CRYSTALLINE FORMS OF COCOA BUTTER PolymorphMelting Range (° C.) I 16-18 II 22-24 III 24-26 IV 26-28 V 32-34 VI34-36

While each of the polymorphs is contemplated to be a useful variant ofthe invention, preferred embodiments will comprise cocoa butter in FormV. The Form V polymorph is solid at room temperature but advantageouslymelts below mouth temperature to provide a smooth mouthfeel andorganoleptically pleasing experience when consumed.

In one embodiment, the fat matrix is provided by the cocoa butter inchocolate. Chocolate that is suitable for use in invention may be eithera solid or liquid at room temperature, but typically will be a solid,and preferably will comprise the Form V polymorph of cocoa butter.However, the term “chocolate” is not limited to any particular polymorphand is not necessarily crystalline. Typically, cocoa butter comprisesfrom about 5% to about 100% of the total fat of the chocolate. Whilemany desirable chocolate products will have cocoa butter contents towardthe upper end of this range, well known advances in chocolate technologyhave allowed substantial amounts of cocoa butter to be replaced by otherfats, including, but not limited to, vegetable oils and the like,without sacrificing the organoleptic, textural, and mouthfeel propertiesof chocolate. With due regard to such advances in chocolate formulation,the compositions of the present invention, in the broadest sense, arenot limited to any particular cocoa butter content. Nonetheless, certaindesirable embodiments favor the use of substantial quantities of cocoabutter. Therefore, various embodiments of the invention presentlycontemplated to be useful include those having from about 10%, 15%, 20%,25%, or 30% to about 70%, 75%, 80%, 85%, or 90% cocoa butter by weightof the total fat content. Exemplary embodiments have a cocoa buttercontent ranging from about 40% to about 100%, about 50% to about 100%,about 60% to about 100%, about 70% to about 100%, about 80% to about100%, and about 90% to about 100% by weight of the total fat content ofthe chocolate. Within the broad range of cocoa butter content (i.e.,from about 5% to about 100% by weight of the total fat content), it iscontemplated that the lower and/or upper limits of that range may beincreased or decreased, respectively, by intervals of about 5%, eachsuch sub-range being contemplated as an embodiment of the invention.

Suitable chocolate may be obtained using any of the various processesknown in the art as described in, for example, The Science of Chocolate,by Stephen T. Beckett, The Royal Society of London (2000), incorporatedby reference in its entirety. The term “chocolate” includes, withoutlimitation, sweet chocolate, semi-sweet chocolate, dark chocolate, milkchocolate, white chocolate, couverture chocolate, baking chocolate, andany of those for which a standard of identity has been established bythe U.S. Food and Drug Administration under 21 C.F.R. §163, Subpart B.Of course, it is within the scope of the invention to include other foodcomponents commonly found in chocolate confections, such as nut meats,nut butters, puffed grains, fruit, soy, caramel, and the like. Suitablechocolate may be obtained using any of the various processes known inthe art as described in, for example, The Science of Chocolate, byStephen T. Beckett, The Royal Society of London (2000), the contents ofwhich are incorporated by reference in its entirety.

In another embodiment, the fat matrix is provided by a so-called“compound coating.” The term “compound coating” refers to any cocoaflavored confectionary product wherein some or all of the cocoa butterof chocolate is replaced with a lauric or non-lauric hard butter, suchas vegetable fat. Suitable compound coatings are well known in the artand include, for example, those disclosed U.S. Pat. Nos. 6,251,448 toDeStephen et al., 5,932,275 to Nalur, and 4,430,350 to Tresser, thecontents of which are incorporated by reference. Other suitable compoundcoatings are described in Chapter 6 of Chocolate, Cocoa, andConfectionery: Science and Technology, by B. W. Minifie, 3^(rd) Edition,the contents of which are incorporated by reference.

The amount and type of vegetable fat may be chosen to vary physicalproperties of the chocolate or compound coating, such as melting pointor hardness. For example, if some of the cocoa butter naturally found inthe cocoa beans is replaced with a cocoa butter replacer (e.g., avegetable oil such as palm kernel oil, coconut oil, or soybean oil), theresulting chocolate or compound coating is softer and the melting pointis reduced. On the other hand, if some of the cocoa butter is replacedwith a cocoa butter equivalent having higher amounts of stearicacid-oleic acid-stearic acid (SOS) moieties than cocoa butter, themelting point is increased. Such techniques of modifying the physicalproperties of chocolate based on fat eutectics are well known in the artand are discussed in detail in The Science of Chocolate, by Stephen T.Beckett, The Royal Society of London, Copyright 2000. A useful meltingpoint range for chocolate according to the present invention is betweenabout 15° C. and about 40° C., more preferably between about 20° C. andabout 39° C., even more preferably between about 32° C. and about 38°C., and most preferred between about 32° C. to about 34° C. The meltingpoint of a compound coating may be higher than that of conventionalchocolate. The higher melting point of compound coating offers theadvantage of stability over a wide range of ambient temperatures. Auseful melting point range for chocolate compound coating according tothe present invention is between about 33° C. and about 49° C., morepreferably between about 35 and about 44° C., even more preferablybetween about 36° C. and about 38° C.

The physical properties of the chocolate may also be varied by changingthe type of cocoa butter that is used or the milk fat content. Forexample, the melting point of chocolate may be varied by judiciouschoice of the type of cocoa butter. As a non-limiting example, whenMalaysian cocoa butter is used, the resulting chocolate has a highermelting temperature than when Brazilian cocoa butter is used.Alternatively, the melting point of the chocolate can be varied bychanging the amount of milk fat. In particular, the melting point of thechocolate may be lowered by increasing the amount of milk fat.

Suitable active agents are not particularly limited and include anysubstance possessing beneficial biological activity to a human. Theactive agent may be a liquid or a solid at ambient conditions. Solidactive agents may suitably be in the form of a powder. The active agentis dispersed substantially homogeneously throughout the chocolate orcompound coating to form a comestible composition with a smooth texture.This may be achieved, for example, by either adding the active agentimmediately before or during the conching step of chocolate production,or during a subsequent molding step. When the active agent is inparticulate form, it is preferred, but not necessary, to add the activeagent during the conching step to ensure that the particles aresubstantially coated with fat. On the other hand, if the active agent issoluble in melted chocolate, or if the active agent cannot be subjectedto physical grinding, the active agent may be blended with the chocolateimmediately prior to the molding step. Such is the case for VitaminD3for example, because it is normally manufactured with a fragileprotective coating that prevents degradation, so that it is not amenableto grinding. If desired, the solubility of the active agent in chocolatemay be increased by combining the active agent with an emulsifier priorto it being added to the chocolate.

In a particularly interesting embodiment, the active agent is inparticulate form, preferably a powder. In the broadest aspects of theinvention, the powder is typically one having a median particle diameterof about 1 to about 25 μm, preferably about 4 to about 15 μm, and morepreferably between about 10 and about 13 μm. Surprising results havebeen obtained with powders having a median particle diameter of about 10μm to about 13 μm. Specifically included within this range are powdershaving an average particle size of about 10 μm, about 11 μm, about 12μm, and about 13 μm. When the average particle size is within the rangeof about 8 and about 12 μm, it has surprising been found that largeamounts of particulate additives may be included without adverselyeffecting the viscosity of the chocolate melt. In this regard, it hasbeen discovered that chocolate and compound coating may be preparedhaving 20% by weight or more, 25% by weight or more, and even 30% byweight or more, calcium carbonate powder having an average particle sizebetween about 10 μm to about 13 μm. The resulting products have atexture and mouthfeel comparable to chocolate or compound coating towhich calcium carbonate powder has not been added.

In other exemplary embodiments, the powder has a median particle size ofabout 2 μm, about 4 μm, about 6 μm, about 8 μm, about 10 μm, about 12μm, about 15 μm, or about 20 μm. The particle size distribution istypically broad. In one embodiment, the particle size distribution has afull-width at half maximum (FWHM) that is at least about 5% of themedian particle size, preferably at least about 15% of the medianparticle size, more preferably at least about 25% of the median particlesize, and even more preferably, at least about 50% of the medianparticle size. In one interesting embodiment, the median particle sizeof the active agent is about 12 μm and the FWHM of the particledistribution is about 5 μm.

The micron-sized powder comprising the active agent may be produced byphysical comminution of an active agent to a desired median particlesize and/or particle size distribution by physical grinding, milling andthe like. Methods are known in the art for producing fine powders,non-limiting examples of which include granulating, hammer milling, jetmilling, ball milling, media milling or grinding by using a mortar andpestle. It is within the ordinary skill in the art to provide powders ofactive agents having any desired median particle size and particle sizedistribution.

In other embodiments, active agents which themselves are not inparticulate form may be converted to particulate form beforeincorporation into the fat matrix. Powders of active agent may beobtained, for example, by applying an active agent to a pharmaceuticallyinert particle support, such as lactose, cellulose, silica and the like.This approach may be desirable, for example, where the required amountof active agent is so small that it becomes difficult to handle or tomeasure accurately. By applying the active agent to a particle support,the active agent becomes spread over a greater amount of material, sothat conventional sample handling or measurement methods can be employedwithout sacrificing a substantial portion of the active agent. Suitably,the active agent is dissolved or suspended in a pharmaceuticallyacceptable liquid or is itself a liquid. The active agent may be appliedto the particle support by any of the methods known in the art forcoating powders, including spray coating or fluidized bed coating. Topromote adhesion of the active agent to the particle support, thepharmaceutically acceptable liquid optionally may contain an adhesionagent. The adhesion agent may be, for example, a pharmaceuticallyacceptable polymer that helps to entrap the active agent on the surfaceof the particle support during the powder coating process or after theliquid has evaporated. Alternatively, the active agent may bemicroencapsulated with a shell material. Techniques for producingmicroencapsulated materials are well know in the art. Powders comprisingmicroencapsulated active agents or active agents dispersed on aparticulate support will have the same median particle size and particlesize distribution described above.

One aspect of this invention is the recognition that it is advantageousto control the particle size range of the particulate active agent inorder to obtain high levels of incorporation of the active agent withouthaving deleterious effects on the texture and organoleptic properties ofthe chocolate or compound coating composition. Without wishing to bebound by any theory, it is believed that when the median particle sizeof a particulate active agent is very small (e.g., below about 10microns), the total surface area of the active agent becomes very large,according to the well known relationship between particle size andsurface area. When this happens, the particulate active agent may not besufficiently coated by the limited amount of fat in the chocolate,resulting in inadequate incorporation of the active agent into thechocolate and/or increase in the viscosity of the chocolate or compoundcoating. On the other hand, when the median particle size of the activeagent is greater than about 15 μm the chocolate or compound coating isperceived as being overly gritty and lacking the smooth texture normallyassociated with chocolate and compound coating. The finding that powdershaving a median particle diameter of about 10-13 μm can be formulatedinto chocolate and compound coatings at high levels is particularlysurprising in light of conventional wisdom which dictates that it isnecessary to provide active agents in the sub-micron range. See e.g.U.S. Pat. No. 4,609,543, which is incorporated by reference in itsentirety.

Another aspect of the invention is therefore to provide high levels ofincorporation of a powder into a fat matrix, such as chocolate orchocolate compound coating, without deleterious effects on the viscosityof melted or liquid matrix. Without wishing to be bound by anyparticular theory, it is believed that the viscosity of melted or liquidchocolate will depend, at least in part, on both the particle size andparticle size distribution of the powder. Small particles present agreater surface area to be solvated by fat. Thus a very large surfacearea of a bulk powder can disrupt the packing of fat molecules due tothe ordering required to fully solvate the powder. Further, when theparticle size distribution of the particulate active agent is verynarrow, the packing of the active agent particles in the fat matrix isinefficient, limiting the amount of active agent which can beincorporated in the chocolate or compound coating. By providing a powderwith a broad particle size distribution, tighter packing of the powderis possible and thus less fat is required to solvate small clusters ofactive agent on a weight basis.

The apparent viscosity of the melted fat matrix, including chocolate orchocolate compound coating, should be within a range suitable forforming solid bars when cooled to room temperature. Typically, theapparent viscosity of the melt will be within ±50%, preferably ±25%,more preferably ±10%, and more preferred still ±5% of the apparentviscosity of comparable fat matrix to which the particulate agent hasnot been added. In some embodiments, the melted chocolate or chocolatecompound coating will have an apparent viscosity of about 500 to about200,000 cP (centipoises), about 1,000 to about 100,000 cP, about 5,000to about 50,000 cP, about 10,000 to about 40,000 cP, or about 15,000 toabout 30,000 cP at 50° C. and a spindle rate of 20 RPM. Typically,although not necessarily, the apparent viscosity of chocolate orchocolate compound coating in the absence of particulate additives suchas calcium carbonate powder will be about 10,000 to about 30,000 cP, andmore typically about 25,000 cP, as measured on a Brookfield viscometermodel DV-11+ using an LV1 spindle operating at 20 RPM at about 56° C. Itwill be recognized however, that due to the large differences inviscosity among the various types of chocolate and chocolate compoundcoating, these values are merely illustrative and are not representativeof all chocolate and chocolate compound coating, or other fat matrices,within the scope of the invention.

In certain embodiments of the invention, the active agent is anutraceutical, such as a vitamin or a substance derived from a plant oranimal source. Non-limiting examples of suitable agents include vitaminsA, B6B12C, D, E, K, thiamin, riboflavin, niacin, folic acid, biotin,pantothenic acid, calcium, phosphorus, iodine, magnesium, zinc,selenium, copper, manganese, chromium, molybdenum, chloride, potassium,boron, nickel, silicon, and vanadium. Nutraceuticals derived from plantsor animals may include, without limitation, aloe, bilberry, blackcohash, chamomile, chasteberry tree, chondroitin, co-enzyme Q10, dongquai, echinacea, evening primrose oil, feverfew, garlic, ginger, gingkobiloba, ginseng, glucosamine, green tea, guarana, hawthorn, horsechestnut, isoflavones, kava-kava, lutein, lycopene, milk thistle,nettle, omega-3 fatty acids, sam-e, St. John's wort, docosahexaenoicacid (DHA) and eicosapentaenoic acid (EPA), saw palmetto, tea tree oil,valerian, and yohimbe, and the like.

Calcium carbonate is a currently preferred active agent according to theinvention. It is well known in the art that calcium carbonate powdershaving a variety of median particle diameters are commerciallyavailable. For example, food grade and USP grade calcium carbonatepowders having median particle diameters ranging from 0.7 to 20 μm areavailable from suppliers such as Omya, Inc. (Alpharetta, Ga.), OmyaArizona, Inc. (Lucerne Valley, Calif.), J. M Huber Corp. (Atlanta, Ga.),and Minerals Technologies Inc. (New York, N.Y.). Suitable calciumcarbonate powders having a median particle size of 15 μm, in someembodiments, may be characterized by a distribution where about 65% ormore of the bulk volume of the powder has a particle size between 5 and25 μm (±66% from the median) and about 40% or more of the bulk volumehas a particle size between about 10 and 20 μm (±33% from the median).Similarly, suitable calcium carbonate powders having a median particlesize of 12 μm, according to one embodiment, may be characterized by adistribution where about 50% or more of the bulk volume of the powderhas a particle size between 4 and 20 μm (±66% from the median) and about30% or more of the bulk volume has a particle size between about 8 and16 μm (±33% from the median). Suitable calcium carbonate powders havinga median particle size of 6 μm, according to one embodiment, may becharacterized by a distribution where about 55% or more of the bulkvolume of the powder has a particle size between 2 and 10 μm (±66% fromthe median) and about 25% or more of the bulk volume has a particle sizebetween about 4 and 8 μm (±33% from the median). Suitable calciumcarbonate powders having a median particle size of 3-4 μm, according toone embodiment, may be characterized by a distribution where about 50%or more of the bulk volume of the powder has a particle size between 1.2and 5.8 μm (±66% from the median) and about 25% or more of the bulkvolume has a particle size between about 2.3 and 4.7 μm (±33% from themedian). Suitable calcium carbonate powders include, but are not limitedto those available from OMYA, Inc. under the tradenames OMYA-Cal FG 15,OMYA-Cal USP 15, OMYA-Cal LL OC FG 15 BTH, OMYA-Cal LL USP 15, OMYA-CalLL USP 15 BTH, OMYA-Cal FG-10AZ, OMYA-Cal FG-6AZ, and OMYA-Cal USP-4AZ.

In other embodiments of the invention, the active agent or particulateactive agent is a pharmaceutical. Non-limiting examples of suitablepharmaceuticals include anti-infectives such as antibiotics andantiviral agents; analgesics and analgesic combinations; local andgeneral anesthetics; anorexics; antiarthritics; antiasthmatic agents;anticonvulsants; antidepressants; antihistamines; anti-inflammatoryagents; antinauseants; antineoplastics; antipruritics; antipsychotics;antipyretics; antispasmodics; birth control preparations, cardiovascularpreparations (including calcium channel blockers, beta-blockers,beta-agonists and antiarrythmics); antihypertensives; diuretics;vasodilators; central nervous system stimulants; cough and coldpreparations; decongestants; diagnostics; hormones; bone growthstimulants and bone resorption inhibitors; immunosuppressives; musclerelaxants; psychostimulants; sedatives; tranquilizers; proteins,peptides and fragments thereof, and the like.

Typically, particulate active agents will be incorporated into chocolateor compound coating at levels between about 0.5% to about 50% on aweight basis. More typically, the active agent will comprise about 1 toabout 30% by weight of the chocolate or compound coating. By practicingthe methods of this invention, it is possible to obtain activeagent-containing chocolate or compound coating confections with a smoothtexture, even if relatively large amounts of active agent are present,for example 20% by weight or more, 25% by weight or more, and even 30%by weight or more. By way of example, a piece of chocolate having atotal weight of about 7 grams will typically, though not necessarily,contain from about 1 mg to about 1,800 mg of active agents.

EXAMPLE 1

The effect of calcium carbonate particle size on the properties ofchocolate compound coating was examined.

Samples A-D were prepared by blending the calcium carbonate powdersshown in FIG. 2 with melted dark compound chocolate (Peters, 33% cocoabutter and butter fat) at a weight ratio of calcium carbonate tocompound chocolate of 1:3.4. The melted compound chocolate/calciumcarbonate mixture was conched and allowed to solidify. The solid mixturewas remelted and Vitamin D3 was blended in at a weight ratio of about1:13 Vitamin D3 to chocolate compound/calcium carbonate mixture. Themelted chocolate compound mixtures containing calcium carbonate andVitamin D3 were molded to form chocolate bars having a weight of 7grams. The chocolate bars nominally contained about 5.1 grams ofchocolate, about 1.5 grams of calcium carbonate powder, and about 400 mgof Vitamin D3.

The chocolate bars corresponding to each of the different size calciumcarbonate powders (samples A-D) were visually inspected by examining theoutside surface of each bar and a cross section of the bar to assess thehomogeneity of the product. The bars were also tasted to determine theeffects of the calcium carbonate and/or Vitamin D3 on the organolepticproperties of the chocolate compound coating. The results are summarizedin Table 2.

TABLE 2 EFFECT OF PARTICLE SIZE ON CALCIUM-FORTIFIED CHOCOLATE COMPOUNDCOATING Median Sample Calcium carbonate Diameter Observations A OMYA-CALFG-4 AZ  4 μm Pasty texture/chalky taste Inhomogeneous B OMYA-CAL FG-6AZ  6 μm Pasty texture/chalky taste Inhomogeneous C OMYA-CAL FG-10 AZ 12μm Smooth/normal chocolate homogeneous D OMYA-CAL FG-15 AZ 15 μm Pastytexture/chalky taste Inhomogeneous

Visual inspection revealed that the calcium carbonate powders havingmedian particle diameters of 4, 6, and 15 microns (samples A, B, and D)did not blend homogeneously with the chocolate compound coating. Regionsof localized calcium carbonate powder inhomogeneity were clearly visibleon the surface and interior of the chocolate bars. Samples A, B, and Dwere described as having a “chalky” taste and a “pasty” mouthfeel notnormally associated with chocolate or chocolate compound coating. Incontrast, sample C, comprising 12 micron median particle diametercalcium carbonate powder, yielded a homogeneous bar with no indicationof localized clumping of calcium carbonate powder. Moreover, thechocolate bar had a mouthfeel and taste substantially identical to thatof a normal (i.e., unfortified) chocolate compound coating.

EXAMPLE 2

The effect of mixing two calcium carbonate powders of differing particlesize on the properties of chocolate compound coating was examined, asshown in Table 3.

TABLE 3 MIXTURES OF CALCIUM CARBONATE POWDERS OF DIFFERENT MEDIANDIAMETERS Median Sample Calcium carbonate Diameter Observations AOMYA-CAL FG-4 AZ  4 μm Pasty texture/chalky (Example 1) tasteInhomogeneous D OMYA-CAL FG-15 AZ 15 μm Pasty texture/chalky (Example 1)taste Inhomogeneous E OMYA-CAL FG-4 AZ ~11 μm  Smooth/normal (1 part) +chocolate OMYA-CAL FG-15 AZ homogeneous (1.5 parts)

Sample E was prepared by blending one part OMYA-CAL FG-4 AZ calciumcarbonate powder (4 μm median particle diameter) and 1.5 parts OMYA-CALFG-15 AZ calcium carbonate powder (15 μm median particle diameter) withmelted dark compound chocolate (Peters, 33% cocoa butter and butter fat)at a weight ratio of 1:1.5:8.5 (OMYA-CAL FG-4 AZ/OMYA-CAL FG-15AZ/chocolate compound coating). The total weight ratio of calciumcarbonate to chocolate compound coating was 1:3.4, as in Example 1. Themixture was conched and allowed to solidify. After solidification, themixture was remelted and combined with Vitamin D3 at a weight ratio of1:12.75 (Vitamin D3 to chocolate compound coating/calcium carbonatemixture). A sample of the mixture was molded to form a 7 gram chocolatebar that nominally contained about 0.6 grams of OMYA-CAL FG-4 AZ, about0.9 grams of OMYA-CAL FG-15 AZ, about 400 mg of Vitamin D3and about 5.1grams of chocolate compound coating.

As in Example 1, the outside surface and cross section of the resultingcalcium-fortified chocolate bar (Sample E) was visually inspected andthe chocolate bar was tasted. Surprisingly, unlike the case where theOMYA-CAL FG-4 AZ and OMYA-CAL FG-15 AZ powders were added alone, theaddition of both powders to the melted chocolate resulted in a chocolatebar that had a homogeneous dispersion of calcium carbonate and a tasteand texture substantially identical to normal, unfortified chocolatecompound coating. It will be observed that the combination of one partOMYA-CAL FG-4 AZ calcium carbonate powder having a 4 μm median particlediameter and 1.5 parts OMYA-CAL FG-15 AZ calcium carbonate powder havinga 15 μm median particle diameter yields a powder having a medianparticle diameter of about 11 μm. The results obtained with the 11 μmpowder were substantially identical to the results obtained with the 12μm powder (Sample C) of Example 1. It is believed that that the 4 μm and15 μm powder could, in the alternative, first be mixed together andsubsequently added to the chocolate compound coating with identicalresults.

EXAMPLE 3 Chocolate Multivitamin

The multivitamin components listed in Table 4 were blended into melteddark compound chocolate (Peters, 33% cocoa butter and butter fat), whichwas subsequently solidified to form a chocolate bar weighing 7 grams.The quantity of each component shown in Table 4 were chosen to be theamounts found in a commercially available Centrum Silver™ multivitamin.The calcium carbonate was OMYA-CAL FG-10 AZ having a median particlediameter of 12 μm.

TABLE 4 CHOCOLATE MULTIVITAMIN Active Agent Amount Source Vitamin A 3500IU Vitamin A acetate, Beta-carotene Vitamin C 60 mg Sodium AscorbateVitamin D 400 IU Ergocalciferol Vitamin E 45 IU D,L-alpha tocopherylacetate Vitamin K 10 mcg Phytonadione Thiamin 1.5 mg Thiamin MononitrateRiboflavin 1.7 mg Riboflavin Niacin 20 mg Niacinamide Vitamin B₆ 3 mgPyrodoxine Hydrochloride Folic Acid 400 mcg Folic Acid Vitamin B₁₂ 25mcg Cyanocobalamin Biotin 30 mcg Biotin Pantothenic Acid 10 mg CalciumPantothenate Calcium 200 mg Calcium Carbonate Phosphorus 48 mg CalciumPhosphate Dibasic Iodine 150 mcg Potassium Iodide Magnesium 100 mgMagnesium oxide Zinc 15 mg Zinc oxide Selenium 20 mcg Sodium selenateCopper 2 mg Cupric oxide Manganese 2 mg Maganese sulfate Chromium 150mcg Chromium chloride Molybdenum 75 mcg Sodium molybdate Chloride 72 mgPotassium chloride Potassium 80 mg Potassium iodide/Potassium chlorideBoron 150 mcg Sodium borate Nickel 5 mcg Nickel sulfate Silicon 2 mgSilicon dioxide/silicon metasilicate Vanadium 10 mcg Sodium metavanadateLutein 250 mcg Lutein Lycopene 300 mcg lycopene

The outside surface and cross section of the chocolate bar was visuallyinspected and the chocolate bar was tasted. Despite the presence of thedifferent components in Table 4, the resulting chocolate bar appearedhomogeneous without localized concentrations of solid components and hada taste and texture substantially identical to normal, unfortifiedchocolate compound coating. The chocolate compound coating effectivelymasked the taste of the vitamin and mineral components.

In some embodiments of the invention, a dietary supplement may compriseone or more of the active agents listed in Table 4.

EXAMPLE 4

The effect of calcium carbonate particle size on the viscosity of meltedsemi-sweet dark chocolate was investigated. For this Example, thesamples were prepared by melting 330 g of chocolate at approximately 56°C. using a water bath. 90 g of calcium carbonate powder was stirred intothe chocolate until uniform. The resulting samples contained about 21%by weight calcium carbonate based on the total weight of thecomposition.

Sample 1 was prepared with calcium carbonate powder having and averageparticle diameter of about 12 μm; Sample 2 was prepared with calciumcarbonate powder having and average particle diameter of about 0.8 μm;and Sample 3 was prepared with calcium carbonate powder having andaverage particle size of 0.07 μm. Sample 3 was selected to berepresentative of the compositions described in U.S. Pat. No. 4,609,543,the contents of which are incorporated by reference.

The viscosity of the melted samples was measured on a Brookfieldviscometer model DV-11+ using the LV1 spindle (operating range of 15 to6,000,000 cP) at temperatures ranging from about 35° C. to about 54.5°C.

The apparent viscosity measurements for Samples 1 and 2 are shown inTable 5.

TABLE 5 Sample 1 Sample 2 20 RPM 2 RPM Spindle Rate Spindle RateTemperature Viscosity Temperature Viscosity (° C.) (cP) (° C.) (cP) 54.518,800 54.6 210,000 49.4 19,600 50.3 215,000 45.5 21,000 45.5 220,00040.7 22,700 40.1 230,000 35.0 27,500 35.0 245,000

Sample 1 was found to have an ideal viscosity for forming molding bars.Bars formed from chocolate comprising 21 weight % of 12 μm calciumcarbonate have a texture substantially identical to chocolate preparedwithout calcium carbonate added. In contrast, the viscosity of Sample 2was too high to form molded bars. It should be noted that the viscositymeasurements for Sample 2 could not be determined at a spindle rate of20 RPM and instead were determined using a spindle rate of 2 RPM, due tothe very high viscosity of the material. Chocolate and chocolatecompound coating are non-Newtonian fluids and therefore the apparentviscosity increases with shear force. As will be evident to the skilledartisan, the apparent viscosity of Sample 2 would be much higher at 20RPM.

It was not possible to measure the viscosity of Sample 3 because it wasfar above the viscosity limits of the viscometer. Even at very lowshear, i.e., about 1 RPM, the apparent viscosity was estimated to beabove 6 million cP. Upon cooling, the compound coating did not solidifyinto a form suitable for preparing molded bars but rather had theconsistency of a soft, sticky, semi-solid.

The invention having been described by the foregoing description of thepreferred embodiments, it will be understood that the skilled artisanmay make modifications and variations of these embodiments withoutdeparting from the spirit or scope of the invention as set forth in thefollowing claims.

1. A dietary supplement comprising a chocolate or chocolate compoundcoating matrix having a melting point between about 35° C. and about 40°C. comprising one or more active agents selected from the groupconsisting of: vitamin A, vitamin C, vitamin D, vitamin E, vitamin K,thiamin, riboflavin, niacin, vitamin B6folic acid, vitamin B12biotin,pantothenic acid, calcium, phosphorus, iodine, magnesium, zinc,selenium, copper, manganese, chromium, molybdenum, chloride, potassium,boron, nickel, silicon, vanadium, lutein, lycopene, iron, tin, ginsengroot, and ginkgo biloba leaf wherein the one or more active agents aredispersed homogeneously throughout the chocolate or chocolate compoundcoating matrix and collectively comprise at least about 20% by weight ofthe chocolate or chocolate compound coating matrix; and wherein theapparent viscosity of the chocolate or chocolate compound coating matrixcomprising the one or more active agents, in the molten state, isbetween about 500 and about 200,000 cP when measured on a spindleviscometer at a spindle rate of 20 RPM at about 56° C.
 2. The dietarysupplement of claim 1, wherein the apparent viscosity of the chocolateor chocolate compound coating matrix comprising the one or more activeagents, in the molten state, is between about 1,000 and about 100,000 cPwhen measured on a spindle viscometer at a spindle rate of 20 RPM atabout 56° C.
 3. The dietary supplement of claim 1, wherein the apparentviscosity of the chocolate or chocolate compound coating matrixcomprising the one or more active agents, in the molten state, isbetween about 5,000 and about 50,000 cP when measured on a spindleviscometer at a spindle rate of 20 RPM at about 56° C.
 4. The dietarysupplement of claim 1, wherein the apparent viscosity of the chocolateor chocolate compound coating matrix comprising the one or more activeagents, in the molten state, is between about 15,000 and about 30,000 cPwhen measured on a spindle viscometer at a spindle rate of 20 RPM atabout 56° C.